Post-reexposure administration of riluzole attenuates the reconsolidation of conditioned fear memory in rats

• Published in: Neuropharmacology 2018-03, Vol.131, p.1-10
• Main Authors: Akagi, Kie, Yamada, Misa, Saitoh, Akiyoshi, Oka, Jun-Ichiro, Yamada, Mitsuhiko
• Format: Article
• Language: English
• Subjects: Contextual fear conditioning; CREB phosphorylation; Extinction; Reconsolidation; Riluzole; Spontaneous recovery
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2017.12.009

Recently, we demonstrated that riluzole, which has been shown to block the glutamatergic system, facilitates fear extinction in rats. Here, we undertook experiments on contextual fear conditioning to clarify the actions of riluzole on the reconsolidation of fear memory in rats. We used the fast-acting benzodiazepine midazolam as a reconsolidation-inhibiting control drug. We demonstrated that riluzole (3 mg/kg) and midazolam (1 mg/kg) impaired the reconsolidation of contextual fear memory. Results from spontaneous recovery experiments also suggested that riluzole attenuated reconsolidation. Indeed, conditioned fear did not recover spontaneously 4 weeks after a short (3 min) reexposure and riluzole administration, whereas it recovered after a long (10 min) reexposure. Using western blotting, we demonstrated that a short reexposure increased the phosphorylation of cyclic adenosine monophosphate response element binding protein significantly in the dorsal part of hippocampus, but not in the medial prefrontal cortex. Interestingly, this phosphorylation was attenuated by riluzole with short reexposure. In addition, bilateral microinjection of riluzole (2 μM/0.2 μl/side) directly into the dorsal hippocampus clearly attenuated the reconsolidation. These findings suggested that the attenuating effect of riluzole on the reconsolidation of fear memory involves, at least in part, the dorsal part of the hippocampus. In conclusion, we demonstrated that riluzole attenuates the reconsolidation of fear memory in rats. •Riluzole with short reexposure attenuates reconsolidation of fear memory in rats.•Fear responses do not recover spontaneously with riluzole after short reexposure.•Behavioral effect of riluzole involves, at least in part, the dorsal hippocampus.